Epstein Barr Virus (EBV) causes mononucleosis, is strongly implicated in Burkitt's lymphoma and nasopharyngeal carcinoma, and may be associated with rheumatoid arthritis. Individuals with these diseases produce antibodies to viral early antigens, capsid antigens, and nuclear antigens. The immune response to EBV antigens has been shown to be an important indicator for clinical evaluation and treatment. However, current immune assays lack sensitivity and selectivity, require expert interpretation, and are not amenable to large-scale clinical studies. Our goal is to improve the clinical diagnostics for EBV related diseases. Genes for EBV antigens were cloned into a high expression plasmid and the corresponding EBV polypeptides were synthesized in bacteria, purified, and used to develop sensitive enzyme linked immunosorbent assays (ELISA) to quantitate antibodies to specific EBV proteins. In the proposed research, these ELISA methods will be used to measure class-specific (IgG, IgA, IgM) antibody titers to EBV antigens in normal individuals and in patients with acute and chronic mononucleosis, Burkitt's lymphoma, nasopharyngeal carcinoma, and rheumatoid arthritis. The specific antibody levels will be correlated with clinical data to determine the efficacy of the ELISA measurements as prognostic indicators. In the initial studies of Phase I, the analysis will be limited to samples from serum banks. If the data support the clinical value of the assays, Phase II studies will entail field trials involving the close collaboration with clinicians.